Personalized collection of plasma from healthy donors: A randomized controlled trial of a novel technology-enabled nomogram.

BACKGROUND: Source plasma is essential to support the growing demand for plasma-derived medicinal products. Supply is short, with donor availability further limited by the coronavirus disease 2019 (COVID-19) pandemic. This study examined whether a novel, personalized, technology-based nomogram was noninferior with regard to significant hypotensive adverse events (AEs) in healthy donors. STUDY DESIGN AND METHODS: IMPACT (IMproving PlasmA CollecTion) was a prospective, multicenter, double-blinded, randomized, controlled trial carried out between January 6 and March 26, 2020, in three U.S plasma collection centers. Donors were randomly assigned to the current simplified 1992 nomogram (control) or a novel percent plasma nomogram (PPN) with personalized target volume calculation (experimental). Primary endpoint was the rate of significant hypotensive AEs. Noninferiority (NI) was tested with a margin of 0.15%. Collected plasma volume was a secondary endpoint. RESULTS: A total of 3443 donors (mean [SD] BMI: 32 [7.74] kg/m2 ; 65% male) underwent 23,137 donations (median [range]: 6 [1-22] per subject). Ten significant hypotensive AEs were observed (six control; four experimental), with model-based AE incidence rate estimates (95% CI) of 0.051% (0.020%-0.114%) and 0.035% (0.010%-0.094%), respectively (p = .58). NI was met at an upper limit of 0.043% versus the predefined margin of 0.15%. There was no statistical difference between total AEs (all AE types: p = .32). Mean plasma volume collected was 777.8 ml (control) versus 841.7 ml (experimental); an increase of 63.9 ml per donation (8.2%; p < .0001). CONCLUSION: This trial showed that a novel personalized nomogram approach in healthy donors allowed approximately 8% more plasma per donation to be collected without impairing donor safety.

Clinical Utility of Autologous Salvaged Blood: a Review.

INTRODUCTION: Autologous salvaged blood, commonly referred to as "cell saver" or "cell salvage" blood, is an important method of blood conservation. Understanding the mechanism of action and summarizing the existing evidence regarding the safety, efficiency, and the relative costs of cell salvage may help educate clinicians on how and when to best utilize autotransfusion. METHODS: This review focuses on issues concerning the quality of red blood cells (RBC), efficiency, and the cost effectiveness relative to autotransfusion. The key considerations of safe use and clinical applicability are described along with the challenges for wider dissemination. RESULTS: Cell salvage can reduce requirements for allogeneic transfusions, along with the associated risks and costs. Autologous salvaged RBCs provide high-quality transfusion, since the cells have not been subjected to the adverse effects of storage as occurs with banked blood. The risks for RBC alloimmunization and transfusion-related infectious diseases are also avoided. With a careful selection of cases, salvaged blood can be more cost effective than donor blood. Cell salvage may have a role in cardiac, major vascular, orthopedic, transplant, and trauma surgeries. However, there remain theoretical safety concerns in cases with bacterial contamination or in cancer surgery. CONCLUSION: In addition to other methods of blood conservation used in patient blood management programs, autologous salvaged blood adds value and is cost effective for appropriate surgical cases. Evidence suggests that autologous salvaged blood may be of higher quality and confer a cost reduction compared with the allogeneic banked blood, when used appropriately.

New-Generation Thromboelastography: Comprehensive Evaluation of Citrated and Heparinized Blood Sample Storage Effect on Clot-Forming Variables.

CONTEXT: - Thromboelastography (TEG) is a whole blood, real-time analyzer measuring the viscoelastic properties of the hemostasis process and allowing for individualized goal-directed therapy. However, routine use of TEG requires validation of sample storage effect on clot parameters. OBJECTIVES: - To establish the minimum time required for equilibration time and the maximum time for sample storage for all commercially available TEG tests for the new-generation TEG 6s and to determine how those times compare with the older generation TEG 5000. DESIGN: - Citrated and heparinized whole blood samples obtained from 20 healthy donors were analyzed for clot parameters at multiple time points for both the TEG 6s and the TEG 5000. Samples were activated with the citrated multichannel cartridge or the platelet-mapping cartridge in the TEG 6s or with recalcified kaolin in the TEG 5000. RESULTS: - All blood samples yielded TEG parameter results within reference ranges and had a tendency toward hypercoagulable profiles with increased storage time. Sample storage resulted in increased platelet inhibition with significant differences at 4 hours in the platelet-mapping cartridge (arachidonic acid percentage of inhibition, P = .002; adenosine diphosphate percentage of inhibition, P = .02). CONCLUSIONS: - For nonemergent cases or in a central laboratory setting, all tests provided reliable results for up to 4 hours in the citrated multichannel cartridge and for 3 hours for platelet function information in the platelet-mapping cartridge. In emergent/urgent situations in which the sample needs to be run immediately, RapidTEG and functional fibrinogen tests may be preferred.

Washing older blood units before transfusion reduces plasma iron and improves outcomes in experimental canine pneumonia.

In a randomized controlled blinded trial, 2-year-old purpose-bred beagles (n = 24), with Staphylococcus aureus pneumonia, were exchanged-transfused with either 7- or 42-day-old washed or unwashed canine universal donor blood (80 mL/kg in 4 divided doses). Washing red cells (RBC) before transfusion had a significantly different effect on canine survival, multiple organ injury, plasma iron, and cell-free hemoglobin (CFH) levels depending on the age of stored blood (all, P < .05 for interactions). Washing older units of blood improved survival rates, shock score, lung injury, cardiac performance and liver function, and reduced levels of non-transferrin bound iron and plasma labile iron. In contrast, washing fresh blood worsened all these same clinical parameters and increased CFH levels. Our data indicate that transfusion of fresh blood, which results in less hemolysis, CFH, and iron release, is less toxic than transfusion of older blood in critically ill infected subjects. However, washing older blood prevented elevations in plasma circulating iron and improved survival and multiple organ injury in animals with an established pulmonary infection. Our data suggest that fresh blood should not be washed routinely because, in a setting of established infection, washed RBC are prone to release CFH and result in worsened clinical outcomes.

Safety of RBC apheresis and whole blood donation in allogeneic and autologous blood donors.

Automated red cell collection is now a well-established technology. As with any new method, the risks and benefits must be weighed against older approaches, in this case manual collection. Although widely perceived to be safe, manual collection is associated with a number of potential complications, some of which can be serious, even debilitating. The safety record of 2-RBC and other RBC automated procedures is excellent. Physiologic, cardiovascular, and neurocognitive responses are modest and fall within those seen for manual collection. The long term effects related to erythropoietic response and iron loss are manageable and are similar to the effects of repeated whole blood donation. The collection of whole blood by manual means has been performed for nearly a century and as result the safety of this procedure is assumed. Conversely, the safety of automated collection in general and particularly RBC has had to "prove" itself, primarily because it is much more recent and is a different paradigm. Millions of procedures have been performed using both approaches. The blood donor, the "raw material" which makes hemotherapy possible, is the essential enabler in these processes. This article examines the complications of both manual and automated RBC collection.

Automation of the glycerolization of red blood cells with the high-separation bowl in the Haemonetics ACP 215 instrument.

BACKGROUND: The FDA has approved a closed-system red blood cell (RBC) glycerolization procedure with the ACP 215 (Haemonetics), which requires a centrifuge to prepare RBCs before and after glycerolization. In the study reported here, the Haemonetics high-separation bowl was evaluated in an attempt to automate these two concentration steps. STUDY DESIGN AND METHODS: Ten units of nonleukoreduced citrate phosphate dextrose (CPD)-anticoagulated whole blood were stored at 4 degrees C for 2 to 6 days before glycerolization and freezing as nonrejuvenated RBCs. Twenty-five units of nonleukoreduced CPD whole blood were stored at 4 degrees C for 2 to 8 days and then biochemically treated with a solution containing pyruvate, inosine, phosphate, and adenine (PIPA) before glycerolization and freezing as indated-rejuvenated RBC. Twenty units of leukoreduced CPD and AS-1 RBCs were stored at 4 degrees C for a mean of 48 days and treated with PIPA solution before glycerolization and freezing as outdated-rejuvenated RBCs. The glycerolized RBCs were frozen for at least 2 weeks at -80 degrees C, deglycerolized in the Haemonetics ACP 215 with the 325-mL bowl, and stored in AS-3 at 4 degrees C for 21 days. RESULTS: It took approximately 50 minutes to glycerolize the nonrejuvenated and rejuvenated RBCs. After freezing, deglycerolization, and postwash storage at 4 degrees C in AS-3 for 2 weeks, the quality was similar to that of RBCs processed by the current FDA-approved method. CONCLUSION: Processing time and need for technical expertise were significantly reduced with the completely automated functionally closed glycerolization procedure with the high-separation bowl in the Haemonetics ACP 215 instrument.

Multicomponent apheresis blood collection in the United States: current status and future directions.

Transfusion medicine in the USA confronts the ongoing challenges posed by a worsening blood supply, regulatory pressure, public pressure for increased safety and cost pressure. Multicomponent apheresis collection (MAC) is a powerful tool for addressing these issues. There are both clinical and operational advantages to MAC. The most important MAC procedures currently performed are platelet and two-red blood cell apheresis. Both procedures are growing in importance to the blood supply as the demand for platelets and red blood cells (RBC) increase. As the demand for safer and more standardized blood components increases, red cell apheresis may possibly become the collection standard.

Transfusion-associated GVHD after fludarabine therapy in a patient with systemic lupus erythematosus.

BACKGROUND: Fludarabine, a purine antimetabolite with potent immunosuppressive properties, has previously been associated with the development of transfusion-associated GVHD (TA-GVHD) in patients with hematologic malignancies. Its role as a risk factor for TA-GVHD in patients without underlying leukemia or lymphoma is uncertain. STUDY DESIGN AND METHODS: A 42-year-old female with refractory lupus nephritis received three monthly cycles of fludarabine (30 mg/m2/day on Days 1-3) and cyclophosphamide (500 mg/m2 on Day 1). Three months after the last dose of fludarabine, she received 2 units of packed RBCs and 6 units of pooled random platelets, none of which were irradiated. Two weeks later, fever, rash, aminotransferase elevations, hyperbilirubinemia, and pancytopenia developed. RESULTS: Marrow biopsy showed severe aplasia and skin biopsy was consistent with GVHD. Allele-level HLA typing on circulating lymphocytes revealed extra HLA alleles not present in her pretreatment sample, but identical to the HLA haplotypes of an unrelated platelet donor. Treatment with antithymocyte globulin, cyclosporine, and prednisone was followed by preparatory conditioning for a PBPC transplant from an HLA-identical sibling, but the patient died of disseminated candidiasis before transplant. CONCLUSIONS: Fludarabine and other purine analogs are increasingly used in the treatment of disorders other than hematologic malignancy, such as autoimmune disease. The occurence of TA-GVHD after fludarabine therapy in a patient with lupus strongly suggests that this drug is sufficiently immunoablative to be an independent risk factor for TA-GVHD. Irradiation of blood components should be considered in all patients who receive fludarabine therapy.

Low-dose total body irradiation followed by allogeneic lymphocyte infusion may induce remission in patients with refractory hematologic malignancy.

Allogeneic stem cell transplantation is curative for certain cancers, but the high doses of chemotherapy/radiotherapy lead to toxicity. Here, we treat patients with refractory cancer with 100 cGy total body irradiation (TBI) followed by infusion of nonmobilized pheresed allogeneic peripheral blood cells. Twenty-five patients, with a median age of 47 years, with refractory cancers were enrolled. Eighteen patients received sibling and 7 received unrelated cord blood cells. Donor chimerism was assessed at weeks 1, 2, 3, 4, and 8 after transplantation. Seven patients with solid tumors received a sibling transplant and 6 received a cord blood transplant; none achieved donor chimerism, but 1 treated at the higher dose level of 1 x 10(8) CD3+ cells/kg had a transient nodal response. Twelve patients with hematologic malignancies were treated; 1 received a cord blood transplant and 11 received sibling donor cells. Nine of these 11 patients achieved donor chimerism, ranging from 5% to 100%. Four patients had sustained complete remission of their cancers, including one patient with transient 5% donor chimerism. The development of chimerism correlated with hematologic malignancy (P <.001), total previous myelotoxic chemotherapy (P <.001), T-cell dose (P =.03), and graft-versus-host disease (P =.01). Tumor response correlated with donor chimerism (P =.01). Engraftment was achieved in patients with hematologic malignancies who had been heavily pretreated, suggesting the degree of immunosuppression may be a determinant of engraftment. Low-dose TBI and allogeneic lymphocyte infusion may induce remission in patients with refractory hematologic malignancy.